Metastable Protein–Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1–VHL System
Yue Wu, Zhen Zhang, Nina J. Hawkins, Weiping Tang, Xuhui Huang · 2026
Read Metastable Protein–Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1–VHL System by Yue Wu, Zhen Zhang, Nina J. Hawkins, Weiping Tang, Xuhui Huang (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13213396.txt.
Description
Yue Wu and four colleagues propose a design principle for PROTAC drugs, based on fleeting protein contacts, in a paper published in two thousand twenty-six. PROTACs destroy disease proteins by bringing them together with the cell's disposal machinery. The brief encounter complex they stabilize is their whole mechanism.
Those metastable interactions are hard to predict and invisible to most modeling tools. The team simulated the kinase RIPK1 meeting the VHL ligase at large scale. A master-equation model mapped the ensemble of temporary contacts. Four distinct interaction modes looked suitable for drug engagement. Different modes preferred different linker designs. The authors argue rational PROTAC design should start from these transient states, not just stable crystal structures.
Catalog record
| CREATOR | Yue Wu, Zhen Zhang, Nina J. Hawkins, Weiping Tang, Xuhui Huang |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 48 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |